Table of ContentsTable of ContentsExpandWhy Do We Still Use Antidepressants?Rewiring the BrainPsychedelic TreatmentTherapy and Lifestyle ChangesWhen Ongoing Treatment Is NeededComorbiditiesSafety of Long-Term Antidepressant UseWhat It All MeansView All
Table of ContentsExpandWhy Do We Still Use Antidepressants?Rewiring the BrainPsychedelic TreatmentTherapy and Lifestyle ChangesWhen Ongoing Treatment Is NeededComorbiditiesSafety of Long-Term Antidepressant UseWhat It All MeansView All
Table of ContentsExpandWhy Do We Still Use Antidepressants?Rewiring the BrainPsychedelic TreatmentTherapy and Lifestyle ChangesWhen Ongoing Treatment Is NeededComorbiditiesSafety of Long-Term Antidepressant UseWhat It All Means
Table of ContentsExpand
Expand
Why Do We Still Use Antidepressants?
Rewiring the Brain
Psychedelic Treatment
Therapy and Lifestyle Changes
When Ongoing Treatment Is Needed
Comorbidities
Safety of Long-Term Antidepressant Use
What It All Means
View All
If you are taking antidepressants, you might wonder just how long you’ll need to keep taking them. Will you need to take antidepressants forever? The short answer is not necessarily, but it’s complicated.
According to the Centers for Disease Control and Prevention (CDC), more than 60% of patients aged 12 and up who were prescribed antidepressants have been taking them for two years or more. Of that population, 14% have been taking them for over 10 years,leading many to question whether these medications are being overprescribed and over-relied on as a standalone treatment.
“In the attempt to normalize depression, I believe the mental health community did a disservice to clients,” said Dr. Emily Donald, a mental health practitioner and counselor atAligned Counseling and Supervision. “We made it all about brain function, and we focused heavily on antidepressants as the primary intervention. However, there is evidence coming to light that depression is more complex than that.”
At a GlanceSo, what role should antidepressants play in your treatment plan? What other options are available, and how do they compare to existing antidepressants? Are there situations where long-term antidepressant use is the best course of action? Antidepressants can be an effective part of a treatment plan, which may also include therapy and lifestyle changes. Other options, like ketamine-derived medications, may also help people who have treatment-resistant depression. How long you need to stay on medication can depend on many factors, so it is best to work with your doctor to determine what’s right for you.
At a Glance
So, what role should antidepressants play in your treatment plan? What other options are available, and how do they compare to existing antidepressants? Are there situations where long-term antidepressant use is the best course of action? Antidepressants can be an effective part of a treatment plan, which may also include therapy and lifestyle changes. Other options, like ketamine-derived medications, may also help people who have treatment-resistant depression. How long you need to stay on medication can depend on many factors, so it is best to work with your doctor to determine what’s right for you.
Most existing FDA-approved antidepressants are designed to either increase the availability ofserotoninornorepinephrine(or both) in the brain. But, in a widely reported study published inMolecular Psychiatryin July 2022, researchers revealed that there isno consistent evidenceto support the idea that low serotonin levels cause depression.
While some news outlets interpreted this as proof that antidepressants don’t work, the new study actually just confirms what mental health professionals have known for decades: the chemical imbalance theory does not adequately explain the complexity of depression.
That doesn’t mean that antidepressants don’t work. Decades of clinical research on the FDA-approved antidepressants available right now along with other studies investigating how and why antidepressants work confirm that antidepressants can provide symptom relief. A 2018 systematic review inThe Lancet, for example, examined 522 clinical trials comprising over 116,000 patients and found that all antidepressants were more effective than placebo in patients withmajor depressive disorder (MDD).
It is worth noting that other reviews have found significant publication bias in antidepressant studies, with trials showing positive results over-represented and negative data often omitted. However, even when correcting for those biases, studies still found that antidepressants worked—just not quite as much as the bias-skewed literature might suggest.
Some researchers have explained this delayed response as aplacebo effector just a general numbing of emotions. However, those theories don’t explain the consistency of results or the synaptic changes that happen in the brains of patients taking antidepressants.
Antidepressants May Rewire Brains to Think More Positively
In a 2017 article inLancet Psychiatry, researchers suggested that antidepressants aren’t just numbing emotions or acting as a placebo for depressed patients. Instead, the benefits might come from changes to brain circuitry.
The human brain is plastic, meaning it constantly adapts to its changing environment and circumstances. It develops new connections and capabilities in response to changing demands. But that also means that stress—such as a negative life event or a depressive episode—can disrupt connections and the function of synapses.
Specifically, “depression is associated with the tendency to perceive social cues as more negative, to preferentially attend to aversive information, and to recall negative more than positive information concerning oneself,” the researchers wrote in theLancet Psychiatryarticle.
What Is the Negativity Bias?
Researchers discovered that at the beginning of treatment, both depressed patients and healthy participants show an increase in the prioritization of positive over negative emotional information when given antidepressants.
This suggests thatSSRIs and SNRIsmight be helping to correct those stress-induced adaptations in the brain. The fact that changes in synapse connections and numbers are subtler and slower to develop may also explain why these antidepressants take a couple of weeks to produce a noticeable effect for most patients.
Ketamine May Soon Fill Gaps in Standard Antidepressant Treatment Outcomes
The synaptic rewiring hypothesis might also partially explain why not all patients seem to respond to standard antidepressants. “Conventional antidepressants change only positive processing of incoming information,” researchers explained.
But if there is no positive information incoming—perhaps because years of chronic depression have resulted in lost friends, lost hobbies, and lost career opportunities—this newfound ability to perceive positive information might not make you feel much different.
That’s where some of the newer antidepressants derived from ketamine might be able to help. While they don’t seem to rewire the brain for positive information processing like SSRIs or SNRIs do, the researchers argued they might help individuals deal with existing negative memories and reduce the negative emotional response that comes with recalling them.
In other words, stressful or traumatic memories might become less distressing and painful to remember.
Other research shows thatketamine-derived drugscan immediately and significantly reduce suicidal ideation along with many other distressing symptoms of depression in some patients.Ketamineand ketamine-derived treatments can induce a noticeable antidepressant effect within two hours, and as much as 71% of patients experience a significant antidepressant response within 24 hours of a single dose.
All of its reported effects are short-lived, often wearing off in a matter of days, but they are still important. With a rapid (albeit short-lived) relief option, this might be a tool to help certain people to not have to be on ongoing SSRIs or SNRIs.
Ketamine for Treatment-Resistant Depression
The Role of Therapy and Lifestyle Changes
Most clinicians suggest that antidepressants should, ideally, be used as just one piece of a multidimensional treatment plan that includes therapy and lifestyle changes. “[Antidepressants] are a very effective tool to help clients feel well enough (and safe enough) to access other, additional, interventions that can provide lasting results without significant side effects,” Dr. Donald argued.
Dr. Stefan Ivantu, a consultant psychiatrist at the London Psychiatric Clinic, concurred and said, “People tend to feel more energetic and motivated after starting antidepressants, which can help them build healthier habits around exercise, diet, and sleep.”
Whatever their specific mechanism of action, clinicians seem to agree that antidepressants are ideally used to help patients develop more long-term strategies for managing their depression.
“We know that things like staying physically healthy, looking after your mental well-being, reducing stress levels, and social support can reduce the likelihood of depression returning, regardless of what type of depression it is,” Dr. Ivantu explained.
The data supports these claims. In meta-analyses of studies comparing antidepressants on their own, in combination with therapy, and treatments using therapy alone, the findings consistently showed that the combination treatment yielded the most significant and most long-lasting results.
Some Cases of Depression Do Require Ongoing Antidepressant Treatment
Even with the advances in antidepressant research and the promising potential of therapy alongside diet and exercise, some patients with severe depression might still need more help.
For people with chronic or severe depression, medication may be needed on a long-term basis. In these cases, antidepressants are often taken indefinitely.—DR. HAROLD HONG
For people with chronic or severe depression, medication may be needed on a long-term basis. In these cases, antidepressants are often taken indefinitely.
—DR. HAROLD HONG
“But for some people, remission may not be possible,” Dr. Hong explained. “In these cases, the focus shifts to symptom management. Even if symptoms can’t be eliminated entirely, they can usually be significantly reduced with treatment.”
Comorbidities Make Identifying Those Cases Complicated
Whether or not you have a severe,difficult-to-treat form of depressioncan be hard to say for certain. Even if you do need lifelong treatment, it may not necessarily need to involve antidepressants. “When treating depression,” Dr. Ivantu argued, “it’s also crucial to identify whether another undiagnosed mental health condition is actually causing the depressive symptoms.”
“Recent studies have shown that approximately 30% of people with ADHD will also develop depression in their lifetime.Once these people receive a diagnosis and treatment for their undiagnosed ADHD, this can dramatically improve their depressive symptoms.”
If you aren’t responding well to antidepressants—or you are, but you aren’t thrilled about the idea of taking them forever—you may want to talk to your doctor about other conditions that might be making it harder to get rid of stubborn depression symptoms.
ComorbidADHDor other psychiatric or neurological conditions aren’t the only ones that can make depression harder to treat. Other chronic health conditions that affect your physical health have also been linked to depression—and treating those underlying conditions has, likewise, been shown toimprove depression symptoms.
Because of how many factors are at play, Dr. Donald argued, “Antidepressants as a lifelong treatment are an oversimplified answer to a complex systemic issue.”
A recent study from the National Institute of Health and Care Research found that as many as 40% of patients taking antidepressants long-term (at least nine months) were able to stop taking them without their depression symptoms relapsing. Of those whose symptoms did relapse, some were able to manage the symptoms without taking medication again.
Of course, this doesn’t mean no one benefits from long-term antidepressant use or that antidepressants aren’t ever needed—but it does suggest that at least some of the people currently taking medication indefinitely could safely stop.
It is important to note, however, that depression tends to be not just episodic, but recurrent. So if someone has suffered a depressive episode, there is a significant risk for recurrence.
If You Do Have to Take Antidepressants Forever, You Will Be OK
Some recent studies suggest long-term antidepressant use may come with side effects previously unknown to scientists. “These risks include an increased risk of gastrointestinal bleeding, especially for SSRI users,” Dr. Hong explained. “Some studies also suggest that compared to non-SSRI users, those taking the medication are at higher risk of dying from breast cancer.” Less life-threatening side effects of long-term use includeemotional numbing, weight gain, and sexual side effects.
As worrying as those risks might sound, antidepressants are still generally considered safe. Moreover, the benefits in cases where ongoing antidepressant use is necessary to keep depression symptoms at manageable levels often outweigh the risks associated with long-term use.
While a study found that patients with breast cancer who also used antidepressants were more likely to die than those who didn’t, it didn’t find that antidepressants made people more likely to develop breast cancer in the first place.
“My biggest concern with longer-term use of medications is discontinuation syndrome, which tends to be a more challenging problem the longer a patient has been taking medication,” saidDr. Danielle Zito, a board-certified psychiatric nurse and mental health advisor at Illuminate Labs.
About 20% of patients develop discontinuation syndrome after abruptly stopping medication. Symptoms can include nausea, insomnia, headaches, and sensory disturbances, among others.
Some also report a return of depression symptoms, but researchers think this may be a relapse of the original depression symptoms rather than medication withdrawal. It is generally recommended that antidepressants be gradually tapered, and for those who do experience discontinuation syndrome, symptoms usually taper off within about two weeks.
What Does All of This Mean for People With Depression?
These mixed messages about how safe or effective long-term antidepressants are along with the overreliance on antidepressants as a standalone treatment may leave people with depression feeling even more defeated.
The message that your brain is not able to function properly without antidepressants [can be] a disempowering one.—DR. EMILY DONALD
The message that your brain is not able to function properly without antidepressants [can be] a disempowering one.
—DR. EMILY DONALD
The reality is that the current SSRIs and SNRIs work for a lot of people, but they also don’t work for a lot of people. Ketamine-derived drugs are showing promise but might not offer the lasting results people with chronic depression need. While short and long-term side effects for all of these are an important consideration, many find the tradeoff worth it for the ability to better manage their depression.
Takeaways
Scientists are still a long way off from understanding exactly how antidepressants are affecting the brain and how they might harness that mechanism of action in a way that makes it more reliably effective for more people.
In the meantime, the best thing you can do if you’re dealing with depression is find a treatment plan that works for you. That will take some trial and error as you work out what type of medication—if any—and for how long, and what type of therapy is most helpful.
Be patient and kind to yourself as you work through this and remember that the decision about what treatment plan works best for you is ultimately yours. Your friends, family, and healthcare providers can provide important guidance and support but you get the final say when it comes to your own mental health.
What’s the Latest in Depression Treatment?
14 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Centers for Disease Control.Antidepressant use among persons aged 12 and over: United States, 2011–2014.
Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA.The serotonin theory of depression: a systematic umbrella review of the evidence.Mol Psychiatry. 2023;28(8):3243-3256. doi:10.1038/s41380-022-01661-0
Cipriani A, Furukawa TA, Salanti G et al.Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.Lancet. 2018 Apr 7;391(10128):1357-1366. doi: 10.1016/S0140-6736(17)32802-7.
Roest AM, de Jonge P, Williams CD, de Vries YA, Schoevers RA, Turner EH.Reporting bias in clinical trials investigating the efficacy of second-generation antidepressants in the treatment of anxiety disorders: a report of 2 meta-analyses.JAMA Psychiatry. 2015;72(5):500. Doi:10.1001/jamapsychiatry.2015.15
Driessen E, Hollon SD, Bockting CLH, Cuijpers P, Turner EH.Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of us national institutes of health-funded trials. Lu L, ed.PLoS ONE. 2015;10(9):e0137864. Doi:10.1371/journal.pone.0137864
Harmer CJ, Duman RS, Cowen PJ.How do antidepressants work? New perspectives for refining future treatment approaches.The Lancet Psychiatry. 2017;4(5):409-418. Doi:10.1016/S2215-0366(17)30015-9
Machado-Vieira R, Baumann J, Wheeler-Castillo C, Latov D, Henter ID, Salvadore G, Zarate CA.The timing of antidepressant effects: A comparison of diverse pharmacological and somatic treatments.Pharmaceuticals(Basel). 2010 Jan 6;3(1):19-41. doi: 10.3390/ph3010019
Karyotaki E, Smit Y, de Beurs DP, et al.The long-term efficacy of acute-phase psychotherapy for depression: a meta-analysis of randomized trials: Review: the long-term efficacy of acute-phase psychotherapy for depression.Depress Anxiety. 2016;33(5):370-383. doi:10.1002/da.22491
Driessen E, Dekker JJM, Peen J, et al.The efficacy of adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression: A systematic review and meta-analysis of individual participant data.Clinical Psychology Review. 2020;80:101886. doi:10.1016/j.cpr.2020.101886
Katzman MA, Bilkey TS, Chokka PR, Fallu A, Klassen LJ.Adult ADHD and comorbid disorders: clinical implications of a dimensional approach.BMC Psychiatry. 2017;17(1):302. doi:10.1186/s12888-017-1463-3
Duffy L, Clarke CS, Lewis G, et al.Antidepressant medication to prevent depression relapse in primary care: the ANTLER RCT.Health Technol Assess. 2021;25(69):1-62. doi:10.3310/hta25690
Opatrny L, Delaney JA ‘Chris’, Suissa S.Gastro-intestinal haemorrhage risks of selective serotonin receptor antagonist therapy: a new look.Br J Clin Pharmacol. 2008;66(1):76-81. Doi:10.1111/j.1365-2125.2008.03154.x
Gabriel M, Sharma V.Antidepressant discontinuation syndrome.CMAJ. 2017;189(21):E747-E747. doi:10.1503/cmaj.160991
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